The objective of this research is to lean more on the role of monoamines in extrapyramidal dysfunctions. The following areas will be studied: 1) Monkeys with surgically induced tremor and hypokinesia will be used as models for studying the antiparkinsonian efficacy of drugs. 2) The imbalance between various monoaminergic neuronal systems during the occurrence of extrapyramidal dysfunction will be studied. We will examine biochemically and histochemically whether aberrations of monoaminergic pre- and postsynaptic monoaminergic neuronal systems are associated with these dysfunctions. 3) Biochemical aberrations of the monoaminergic neuronal systems will be studied in mutant mice. In these studies we will determine whether the biochemical aberrations occur prior to the phenotypic expression of the disorder. 4) The effects of acute and chronic treatment with several DA agonists on the peripheral and central adrenergic systems will be studied. We will test whether during chronic treatment compensatory mechanisms such as tolerance develop. 5) The therapeutic efficacy of various DA agonists in Parkinsonian patients will be further studied. We will determine whether changes in plasma levels of various hormones and/or putative neurotransmitters reflect (a) the therapeutic effectiveness of DA agonists (b) the occurrence of IM (c) the occurrence of the "on-off" phenomenon.